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Biomedical subjects

C Giannini

Publications and source records attributed to C Giannini.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia.

OBJECTIVE: To investigate the possible role of HCV variants in the pathogenesis of mixed cryoglobulinemia. SETTING: Medical service (rheumatology and hepatology units) of urban, university-affiliated teaching hospitals. DESIGN: Analysis of viral genotypes in a cohort of patients with hepatitis C virus (HCV) infection and mixed cryoglobulinemia. PATIENTS: 90 unselected HCV-positive (anti-HCV antibody-positive and HCV RNA-positive) patients consecutively recruited at routine ambulatory visits: 29 with and 61 without (control group) mixed cryoglobulinemia. MEASUREMENTS: Clinical and histologic data; HCV RNA detection in serum and peripheral blood mononuclear cells by polymerase chain reaction (PCR); HCV genotype determination by two methods based on genotype-specific primer PCR and genotype-specific probe hybridization, respectively. RESULTS: Persistent aminotransferase increases were found in 55% of patients with mixed cryoglobulinemia. Peripheral blood mononuclear cells were infected in 80% of cases. In serum samples, HCV genotype 2a/III was detected with a higher prevalence in patients with mixed cryoglobulinemia than in controls (41% compared with 15%). The overall prevalence of genotype 2a/III in mixed cryoglobulinemia increased to 52% when findings in peripheral blood mononuclear cells were also considered. Among patients with mixed cryoglobulinemia, this genotype was more frequent in those without clinical and biochemical signs of liver disease (85%) or with serum autoantibodies (75%). CONCLUSIONS: Mixed cryoglobulinemia may be related, at least in part, to the HCV genotype infecting the host.

Aged↗
PubMed1996

Chronic hepatitis C and B-cell non-Hodgkin's lymphoma.

Hepatitis C virus (HCV), a hepatotropic and lymphotropic virus, is the major causative agent of nonA-nonB chronic hepatitis; moreover, it is frequently associated with benign and malignant lymphoproliferative disorders such as mixed cryoglobulinaemia and B-cell non-Hodgkin's lymphoma (NHL). We investigated the clinical and virological features of B-cell NHL complicating chronic hepatitis C in a series of 10 patients (M/F 1/9; mean age 63 +/- 6SD years). The malignancy appeared after median 8 +/- 4SD years from onset and was low-grade in six patients, intermediate in three, and high-grade in one. 'One-tube nested' PCR detected serum HCV RNA and viral ongoing replication in both fresh and cultured peripheral lymphocytes in all ten. Analysis of HCV genotypes showed a relatively higher prevalence of 2a/III type compared with unselected chronic hepatitis C (50% vs. 15%). In one patient, HCV RNA was also found in the neoplastic bone marrow and lymph-node specimens. B-cell NHL can complicate chronic hepatitis C and affect the overall prognosis of the disease. The increasing frequency of chronic hepatitis C worldwide suggests that the actual prevalence of this complication may be underestimated. Careful clinical work-up at diagnosis and during follow-up is particularly recommendable.

Aged↗
PubMed1996

Pathologic alterations in the diabetic neuropathies of humans: a review.

Pathologic study of nerve tissue is especially useful for the recognition of interstitial events such as inflammation or vascular alterations that cannot be inferred from clinical or electrophysiologic findings and may provide insight into an underlying mechanism or cause. Considerable variation in the natural history and pathologic alterations among diabetic neuropathies suggests that they are heterogeneous. For diabetic polyneuropathy, two mechanisms need to be considered. The first assumes that hyperglycemia induces metabolic derangements that directly affect Schwann cells (or myelin), nodes of Ranvier, or axons. The second assumes that hyperglycemia and metabolic derangement affect the structure and function of endoneurial microvessels, which then induce fiber changes by altering the blood-nerve barrier, inducing hypoxia or ischemia, or by unknown mechanisms. In proximal diabetic neuropathy, there is increasing evidence that the characteristic lesion is an inflammatory (immune) vasculitis that induces ischemic nerve fiber degeneration. Truncal radiculopathy may be due to an inflammatory polyganglionopathy. In cranial nerve III neuropathy, the monophasic course and the pathologic alterations of ischemia suggest that localized vasculitis should be excluded in future cases. Many upper limb mononeuropathies in diabetes mellitus are from carpal tunnel syndrome. Repetitive shear forces, anatomic factors, and excessive stiffness of connective tissues may cause these mononeuropathies.

Atrophy↗
PubMed1996

Pigmented villonodular synovitis of the spine: a clinical, radiological, and morphological study of 12 cases.

Cases of pigmented villonodular synovitis (PVNS) that affect the axial skeleton are rare and thus information regarding its natural history, treatment, and prognosis remains limited. To characterize this lesion more fully, the authors reviewed their experience with 12 cases of PVNS of the spine (one of which had been previously reported), then reviewed the 11 cases that previously had been reported, and obtained additional follow-up data in six of them. On the basis of the cumulative data provided by these 22 cases, PVNS of the spine appears to occur over a wide range of ages (21-81 years) and, contrary to what was previously suggested, does not show definite gender predilection (12 women and 10 men). The lesion affects the posterior elements of the vertebrae at all levels and involves the facet joints in 89% of cases. Extension into the epidural spine is frequent (70%). Surgical resection appears to be the treatment of choice. Although PVNS of the spine tends to recur locally (18%), repeat surgical excision appears to be curative.

Adult↗
PubMed1996

Cytoskeletal changes in cultured human fibroblasts following exposure to 2,5-hexanedione.

In the present study, the effects of the 2,5-hexanedione (HD) on the various cytoskeletal components of human eukaryotic cells were investigated. Primary cultures of human fibroblasts from three healthy donors were exposed to 2.8 mM HD for 14 days; unexposed cultures were used as controls. At different time intervals, cells were counted and the growth curves compared. After 14 days of treatment, the cultures were processed for immunoblotting, immunocytochemistry and ultrastructural studies. As compared to controls, morphological abnormalities induced by HD consisted of modification of the cell shape, formation of tangles composed by 10 nm filaments and cytoplasmic segregation of microtubules and membrane-bound organelles. By immunocytochemistry, the tangles of cytoplasmic filaments were stained by an antibody specific for vimentin. By immunoblotting, the anti-vimentin antibody recognized only bands of 50-60 kDa. Comparison of growth curves between treated and control fibroblasts clearly revealed an interference of HD with the cell cycle. The present results demonstrate that the cytotoxicity of HD is not restricted to intermediate filaments, but affects other cytoskeletal components, such as microtubules, as suggested by the impairment of cell division cycle.

Cell Count↗
PubMed1995

Basement membrane reduplication and pericyte degeneration precede development of diabetic polyneuropathy and are associated with its severity.

In a recent paper, we showed that the number of endoneurial microvessels per square millimeter and the average luminal area and size distribution of these microvessels are not significantly different in sural nerves of patients with diabetes mellitus as compared to control subjects. Mural area, especially the component due to basement membrane reduplication and cellular debris, was unequivocally increased in diabetes mellitus. Because these latter changes are associated with a decrease in periendothelial cell area, we hypothesized that cellular degeneration, especially of pericytes, may account for basement membrane reduplication and increased frequency of cellular debris. In the present study, we showed that endoneurial microvessels undergo a statistically significant increase in basement membrane area, mural area, and frequency of cellular debris in diabetics without polyneuropathy and an even greater increase in diabetics with polyneuropathy. We also found that duration of diabetes mellitus was significantly associated with area occupied by reduplicated basement membrane and cellular debris, but not with mural and periendothelial area. None of the examined measurements was associated with age. Since the microvessel abnormalities we describe are already present before the development of polyneuropathy and increase with severity of polyneuropathy, it is likely that they reflect functional derangements of pericytes and microvessel function which precede and might be implicated in fiber degeneration.

Analysis of Variance↗
PubMed1995

Hepatitis C virus infection of mononuclear cells from peripheral blood and liver infiltrates in chronically infected patients.

The mechanisms underlying chronicity of hepatitis C virus (HCV) infection are poorly understood, but the importance of impaired viral clearance by the immune system has been suggested. The prevalence of HCV infection of peripheral blood mononuclear cells (PBMC) was in investigated in 34 persistently infected patients with anti-HCV (7 with liver cirrhosis, 10 with chronic active hepatitis, 5 with chronic persistent hepatitis, 4 with chronic lobular hepatitis, and 8 healthy carriers) by polymerase chain reaction (PCR). HCV infection of 116 T cell clones derived from liver infiltrating mononuclear cells obtained from 3 patients with chronic liver disease was examined using the same methods. HCV genomic sequences were found in fresh, unstimulated PBMC from 20 patients with cirrhosis, and chronic active and persistent hepatitis, but in none of the healthy carriers and only in mitogen-activated cells from 1 out of 4 patients with autoresolving chronic lobular hepatitis. Active PBMC infection was confirmed by identification of anti-genomic HCV sequences in the majority of HCV RNA-positive cells (fresh or mitogen-stimulated). A high percentage of T cell clones obtained from liver infiltrates were found to be infected by HCV. These findings suggest that HCV infection of lymphatic cells plays a role in the pathogenesis of chronically evolving liver damage. PBMC may represent a reservoir for latent infection and a site for viral multiplication.

Alanine Transaminase↗
PubMed1995

Polyneuropathy associated with nerve angiomatosis and multiple soft tissue tumors. A newly recognized syndrome.

We report the case of a 33-year-old woman affected by a severe sensorimotor polyneuropathy and multiple soft tissue tumors since childhood. In the biopsied sural nerve, there was a striking vascular proliferation of small vessels. Three subcutaneous nodules were biopsied and disclosed pathologic findings resembling those found in tumors in infantile myofibromatosis. One of the three biopsied subcutaneous nodules was intimately contiguous with a peripheral nerve. The ultrastructural features and immunohistochemical reactivity of the soft tissue tumors and the vessels proliferating in the nerve suggested a common cellular differentiation. The finding of a diffuse polyneuropathy associated with widespread angiomatosis in nerve and multiple soft tissue tumors suggests that these are not coincidental findings, but a manifestation of a syndrome perhaps not previously recognized.

Adult↗
PubMed1995

Comparative analysis of two assays for genotyping hepatitis C virus based on genotype-specific primers or probes.

BACKGROUND/AIMS: The importance of determining the hepatitis C virus genotype has increased since several authors have described a good correlation between hepatitis C virus genotype and response to interferon treatment or to disease severity. It is thus of particular importance to develop reliable assays for hepatitis C virus genotyping. METHODS: We have comparatively analyzed hepatitis C virus genotypes of 208 French and Italian chronically infected patients using genotype-specific primers polymerase chain reaction in the capsid region and a genotype-specific probe-based assay in the 5' untranslated region (LiPA). RESULTS: We found a good concordance between the two assays for the prevalent genotypes in our regions (145/174). The nucleotide sequences in the 5'UTR and capsid domain were investigated to determine the molecular basis of some discordant results. This analysis showed that the genotype-specific probe-based assay gave more consistent results, probably because this technique is based on several probes distributed along the 5'UTR to reveal each genotype. In contrast, the low variability of 5'UTR did not always permit classification of the hepatitis C virus genotype 1 subtypes. We also found some problems, using genotype-specific primers polymerase chain reaction, for less represented genotypes; in particular, in the presence of type 2a/III we obtained more discordant results. This observation is of importance in view of the potential association of this genotype with mild liver disease and a good response to interferon-a treatment.

Base Sequence↗
PubMed1994

Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus.

We evaluated 433 transversely sectioned microvessels from 54 sural nerves of diabetic patients with (43) and without (11) polyneuropathy and compared the findings with those of 366 microvessels from 50 sural nerves from controls, spanning the same ages. Whereas the number of microvessels per square millimeter and lumen areas and their size distribution were not significantly different between diabetic patients and controls, striking changes of the vessel wall were found in the nerves of diabetic patients. Mural area containing reduplicated basement membranes and pericyte degeneration were significantly increased in diabetic when compared with control nerves. A very low frequency of microvessel degeneration and endothelial cell separation was also encountered but only in diabetics with polyneuropathy. The microvessel changes we have found in nerve largely confirm and strengthen our previous findings. This study provides additional strong support for the idea that the mural changes of endoneurial microvessels do not relate to aging but do relate to diabetes mellitus. The structural alterations of endoneurial microvessel mirror changes seen in diabetic retinopathy and are sufficiently severe that they may accompany and account for functional alterations of the blood-nerve barrier and endoneurial microenvironment. It remains to be shown whether and how these changes relate to the development of polyneuropathy.

Adult↗
PubMed1993

Human peripheral nerve macrophages in normal and pathological conditions.

We investigated, by immunocytochemistry and immune electron microscopy, the immunophenotype, morphology and functional properties of human peripheral nervous system (PNS) macrophages (M phi) under normal and pathological conditions. Endoneurial M phi disclosed an elongated, ramified morphology, with the main processes oriented along the major axis of nerve fibers; they shared several lineage-related and functional markers with monocyte/macrophages and central nervous system (CNS) microglia, including CD4, CR3, CR4 and FcRIII. In addition, basal expression of HLA-DR antigens was exclusively confined to M phi in normal PNS. In the course of unrelated pathological conditions, resident M phi underwent activation with transformation to hypertrophic cells or foamy phagocytes and up-regulation of the markers expressed in normal conditions; new expression of a macrophagic antigen was detected on activated M phi. In different neuropathies, HLA-DR expression was also detected on non-myelin forming Schwann cells with ultrastructural features indicative of denervation. The present results demonstrate that the human PNS is provided with an intrinsic population of immunocompetent and potentially phagocytic M phi, which represent the peripheral counterpart of CNS microglia.

Adolescent↗
PubMed1993

Ultrastructural morphometric features of human sural nerve endoneurial microvessels.

We studied the morphometric features of 366 transversely sectioned endoneurial microvessels in sural nerves from 50 healthy volunteers (mean age 34.5 +/- 15.8, range 20 to 66 years). Nerves were obtained and processed by the same techniques and standards used to study biopsied nerves from patients with neuropathy. Endothelial area, basement membrane area, number of endothelial nuclei and junctions, and number of periendothelial nuclei all increase significantly with vessel size as judged by mural area. Periendothelial cell coverage of endothelial perimeter does not correlate with vessel size. Components of endoneurial microvessels, specifically the area containing basement membrane, do not change significantly with age. The present report provides a detailed characterization of the ultrastructural features of endoneurial microvessels with age in humans and provides optimal reference values for study of microvessel pathologic changes in disease.

Adult↗